Adipokines, C-reactive protein and Amyotrophic Lateral Sclerosis \u2013 results from a population- based ALS registry in Germany

Gabriele Nagel,Raphael S Peter,Raphael S Peter,Wolfgang Koenig,Albert C Ludolph,Luc Dupuis,Luc Dupuis,Angela Rosenbohm,Dietrich Rothenbacher,Dietrich Rothenbacher

doi:10.1038/s41598-017-04706-5

Abstract

To investigate the associations of leptin, adiponectin and high-sensitive (hs) C-reactive protein (CRP) with risk and prognosis of amyotrophic lateral sclerosis (ALS). Data from a population-based case-control study in Southern Germany (10/2010–6/2014) of 289 ALS patients (mean age of 65.7 (SD 10.5) years, 59.5% men) and 506 controls were included. During median follow-up of 14.5 months of 279 ALS patients 104 (53.9% men, 68.9 (10.3) years) died. Serum samples were measured for leptin, adiponectin and hs-CRP. Conditional logistic regression was used to estimate ALS risk. Survival models were used to appraise the prognostic value. ALS patients were characterized by lower levels of school education, BMI and smoking prevalence. Adjusted for covariates, leptin was inversely associated with ALS risk (top vs. bottom quartile: OR 0.49; 95% CI 0.29–0.80), while for adiponectin a positive association was found (OR 2.89; 95% CI 1.78–4.68). Among ALS patients increasing leptin concentrations were associated with longer survival (p for trend 0.002), while for adiponectin no association was found (p for trend 0.55). For hs-CRP no association was found. Leptin and adiponectin, two key hormones regulating energy metabolism, were strongly and independently related with ALS risk. Leptin levels were further negatively related with overall survival of ALS patients.

Highlights

These studies suggest that an alteration of energy metabolism might be an important driving force in amyotrophic lateral sclerosis (ALS)
The objective of the present study was to analyze the associations of leptin, adiponectin and hs-C-reactive protein (CRP) as biomarkers of energy metabolism and systemic low-level inflammation with the risk of ALS in a population-based case-control study conducted in southern Germany after controlling for potential confounders
In relation to energy metabolism, it is noteworthy that ALS patients displayed lower Body mass Index (BMI), and higher frequency of physical intense occupational working history

Summary

Introduction

These studies suggest that an alteration of energy metabolism might be an important driving force in ALS. Leptin secretion is generally positively correlated with size of the lipid droplet of the adipocyte[23], while adiponectin levels are decreased with adiposity[23]. Both of these adipokines signal in the hypothalamus to trigger antagonistic effects, ie satiety and increased energy expenditure for leptin, and weight loss and increased energy intake for adiponectin[23]. The objective of the present study was to analyze the associations of leptin, adiponectin and hs-CRP as biomarkers of energy metabolism and systemic low-level inflammation with the risk of ALS in a population-based case-control study conducted in southern Germany after controlling for potential confounders. In patients with ALS the prognostic value of the respective blood markers for overall survival was investigated in a cohort approach

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Conclusion